A kilonova as the electromagnetic counterpart to a gravitational-wave source.

Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

Super-cooled and amorphous lipid-based colloidal dispersions for the delivery of phytosterols.

Super-cooled and amorphous lipid-based colloids are highly desirable delivery systems because of their ability to encapsulate compounds in a soluble or in a non-crystalline state. In this study, we demonstrate the preparation and characterization of super-cooled and amorphous lipid-based nanoscale colloidal dispersions containing high concentrations of phytosterols (PSs). PSs are highly hydrophobic natural bioactive compounds that are known to significantly reduce blood cholesterol levels in humans, but are insoluble in water and are poorly soluble in common lipids such as triacylglycerols (TAGs). Using the ultrahigh pressure homogenization of pre-heated dispersions, followed by temperature quenching, colloidal dispersions with varying concentrations of PSs in the lipid phase are prepared. Long and medium chain TAGs in combination with a non-ionic surfactant are used. The particle size, morphology and stability are analysed by dynamic and static light scattering, electron microscopy, and X-ray diffraction. Rapid temperature quenching enables the formation of stable colloidal dispersions of 10 wt% PSs, more than five times the equilibrium solubility at room temperature. Super-cooled emulsions are formed using liquid TAG, whereas amorphous particles are formed in the case of solid TAG. In both cases, the complete suppression of the crystallization of both PSs and lipids is observed due to the nanoscale confinement. The colloidal dispersions are stable for at least four months. The insights of this work will help understand the colloid formation and particle morphology control in the development of delivery systems for hydrophobic bio-actives such as drugs, cosmeceuticals, nutraceuticals, nutritional and agricultural nanoscale formulations.

A Method for Investigating "Instructional Familiarity" and Discerning Authentic Learning.

BACKGROUND: Presently, most medical educators rely exclusively on item difficulty and discrimination indices to investigate an item's psychometric quality and functioning. We argue "instructional familiarity" effects should also be of primary concern for persons attempting to discern the quality and meaning of a set of test scores. AIM: There were four primary objectives of this study: (1) Revisit Haladyna and Roid's conceptualization of "instructional sensitivity" within the context of criterion-referenced assessments, (2) provide an overview of "instructional familiarity" and its importance, (3) reframe the concept for a modern audience concerned with medical school assessments, and (4) conduct an empirical evaluation of a medical school examination in which we attempt to investigate the instructional effects on person and item measures. SUBJECTS AND METHODS: This study involved a medical school course instructor providing ratings of instructional familiarity (IF) for each mid-term examination item, and a series of psychometric analyses to investigate the effects of IF on students' scores and item statistics. The methodology used in this study is based primarily on a mixed-method, "action research" design for a medical school course focusing on endocrinology. Rasch measurement model; correlation analysis. RESULTS: The methodology presented in this article was evidenced to better discern authentic learning than traditional approaches that ignore valuable contextual information about students' familiarity with exam items. CONCLUSIONS: The authors encourage other medical educators to adopt this straightforward methodology so as to increase the likelihood of making valid inferences about learning.

Leukocyte Gene Expression in Patients with Medication Refractory Depression before and after Treatment with ECT or Isoflurane Anesthesia: A Pilot Study.

Objective. To evaluate leukocyte gene expression for 9 selected genes (mRNAs) as biological markers in patients with medication refractory depression before and after treatment with ECT or isoflurane anesthesia (ISO). Methods. In a substudy of a nonrandomized open-label trial comparing effects of ECT to ISO therapy, blood samples were obtained before and after treatment from 22 patients with refractory depression, and leukocyte mRNA was assessed by quantitative PCR. Patients' mRNAs were also compared to 17 healthy controls. Results. Relative to controls, patients before treatment showed significantly higher IL10 and DBI and lower ADRA2A and ASIC3 mRNA (P < 0.025). Both ECT and ISO induced significant decreases after treatment in 4 genes: IL10, NR3C1, DRD4, and Sult1A1. After treatment, patients' DBI, ASIC3, and ADRA2A mRNA remained dysregulated. Conclusion. Significant differences from controls and/or significant changes after ECT or ISO treatment were observed for 7 of the 9 mRNAs studied. Decreased expression of 4 genes after effective treatment with either ECT or ISO suggests possible overlap of underlying mechanisms. Three genes showing dysregulation before and after treatment may be trait-like biomarkers of medication refractory depression. Gene expression for these patients has the potential to facilitate diagnosis, clarify pathophysiology, and identify potential biomarkers for treatment effects.

Reliability and validity of the Child and Adolescent Trial for Cardiovascular Health (CATCH) Food Checklist: a self-report instrument to measure fat and sodium intake by middle school students.

OBJECTIVE: To develop a scoring algorithm and evaluate the reliability and validity of scores from the Child and Adolescent Trial for Cardiovascular Health (CATCH) Food Checklist (CFC) as measures of total fat, saturated fat, and sodium intake in middle school students. DESIGN: Randomized, controlled trial in which participants were assigned to 1 of 3 study protocols that varied the order of CFC and 24-hour dietary recall administration. Criterion outcomes were percent energy from total fat, percent energy from saturated fat, and sodium intake in milligrams. SUBJECTS/SETTING: A multiethnic sample (33% ethnic and racial minorities) of 365 seventh-grade students from 8 schools in 4 states. STATISTICAL ANALYSES: Multivariable regression models were used to calibrate the effects of individual food checklist items; bootstrap estimates were used for cross-validation; and kappa statistics, Pearson correlations, t tests, and effect sizes were employed to assess reliability and validity. RESULTS: The median same-day test-retest reliability kappa for the 40 individual CFC food items was 0.85. With respect to item validity, the median kappa statistic comparing student choices to those identified by staff dietitians was 0.54. Test-retest reliability coefficients ranged from 0.84 to 0.89 for CFC total nutrient scores. Correlations between CFC scores and 24-hour recall values were 0.36 for total fat, 0.36 for saturated fat, and 0.34 for sodium; CFC scores were consistent with hypothesized gender differences in nutrient intake. APPLICATIONS/CONCLUSIONS: The CFC is a reliable and valid tool for measuring fat, saturated fat, and sodium intake in middle school students. Its brevity and ease of administration make the CFC a cost-effective way to measure middle school students' previous day's intake of selected nutrients in school surveys and intervention studies.

Construction and field validation of a self-administered screener for testosterone deficiency (hypogonadism) in ageing men.

To design a self-administered screening questionnaire to inform men about their risk for testosterone deficiency. The screener was developed in two phases. First was a construction phase in which relevant risk factors and a scoring algorithm were defined from multiple logistic regression analyses of survey data. In the second phase, the screener's accuracy (based on sensitivity, specificity, and Receiver Operating Characteristic (ROC) curves) was tested using patients from a primary care clinic. All subjects provided blood samples for endocrine testing. Survey data from 1660 men aged 40-79 years participating in the Massachusetts Male Ageing Study (MMAS) were analysed in the first phase. The clinic sample consisted of 304 men aged 40-79 years presenting at a large Massachusetts primary health care clinic for routine check-ups or minor medical problems. The primary outcome was testosterone deficiency, defined as serum total testosterone below 12.1 nmol/l. Self-reported variables considered as potential risk factors included age, obesity, chronic diseases, health behaviour, the Jackson dominance scale, and symptoms of stress. The prevalence of testosterone deficiency was 20.4% in the MMAS and 42.1% in the clinic sample. An eight-item screener was developed based on age, body mass index, diabetes, asthma, headaches, sleep patterns, dominance preferences, and smoking status. The screener performed significantly better than chance in identifying men with low testosterone levels; the area under the ROC curve was 0.66 in the MMAS sample and 0.67 in the clinic sample. The self-scored screener developed in this study reliably detects men at risk of hypogonadism. The screener encourages at risk men to seek professional evaluation of their testosterone levels.

Distinguishing between quality of life and health status in quality of life research: a meta-analysis.

Despite the increasing acceptance of quality of life (QOL) as a critical endpoint in medical research, there is little consensus regarding the definition of this construct or how it differs from perceived health status. The objective of this analysis was to understand how patients make determinations of QOL and whether QOL can be differentiated from health status. We conducted a meta-analysis of the relationships among two constructs (QOL and perceived health status) and three functioning domains (mental, physical, and social functioning) in 12 chronic disease studies. Instruments used in these studies included the RAND-36, MOS SF-20, EORTC QLQ-30, MILQ and MQOL-HIV. A single, synthesized correlation matrix combining the data from all 12 studies was estimated by generalized least squares. The synthesized matrix was then used to estimate structural equation models. The meta-analysis results indicate that, from the perspective of patients, QOL and health status are distinct constructs. When rating QOL, patients give greater emphasis to mental health than to physical functioning. This pattern is reversed for appraisals of health status, for which physical functioning is more important than mental health. Social functioning did not have a major impact on either construct. We conclude that quality of life and health status are distinct constructs, and that the two terms should not be used interchangeably. Many prominent health status instruments, including utility-based questionnaires and health perception indexes, may be inappropriate for measuring QOL. Evaluations of the effectiveness of medical treatment may differ depending on whether QOL or health status is the study outcome.

Single-layer continuous colon and rectal anastomosis using monofilament absorbable suture (Maxon): study of 500 cases.

PURPOSE: The study purpose was to evaluate the results of continuous, single-layer colon and rectal anastomoses using a monofilament absorbable suture material (Maxon). METHODS: Four hundred ninety-two consecutive patients undergoing five hundred colon and rectal anastomoses with the above technique were evaluated for outcome, including anastomotic leakage, stricture, and other complications, by means of chart review. RESULTS: Three patients (0.6 percent) died after surgery and 7 (1.4 percent) developed clinical evidence of anastomotic leakage. Twenty-four percent developed some postoperative complications, most of which were minor. CONCLUSIONS: Continuous, single-layer colorectal anastomosis using monofilament absorbable suture can be performed safely, quickly, and with a favorable cost ratio. Handsewn anastomoses should still be part of the armamentarium of the well-trained surgeon.

Influence of organic modifier concentration on plate number in micellar electrokinetic chromatography. 1. 2-propanol.

This paper establishes a physicochemical basis for the efficiency losses in micellar electrokinetic chromatography in buffers containing sodium dodecyl sulfate (SDS) and 2-propanol (2PN). Weakly, intermediately, and strongly retained analytes were separated in phosphate/borate buffers containing 50 mM SDS and from 0 to 10% 2PN by volume. Their plate numbers N generally agreed well with predictions of a theory for N based on longitudinal diffusion and instrumental contributions to dispersion. The N's of weakly and intermediately retained analytes were not affected strongly by 2PN over this concentration range, because their diffusion coefficients varied inversely with buffer viscosity and their retention times largely varied directly with viscosity. These combined effects on dispersion almost canceled. However, the N's of strongly retained analytes decreased with increasing 2PN, because their diffusion coefficients varied inversely with viscosity but their retention times increased more rapidly than did viscosity. These combined effects on dispersion did not cancel. These differences occurred because 2PN penetrated the micelles, caused bound counterions to be released, and increased the micellar charge and electrophoretic mobility. As 2PN concentration increased, the micelles electrophoresced increasingly rapidly against the electroosmotic flow. Consequently, strongly retained compounds required increasingly long times to elute.

Calcium modulation of activation and desensitization of nicotinic receptors from mouse brain.

The effects of extracellular calcium on functional properties of nicotinic receptors from mouse thalamus were investigated. Previous studies have reported that calcium modulates the function of several neuronal nicotinic receptors. A 86Rb+ ion efflux assay was developed to measure nicotinic receptor function from brain tissue, and data indicate that alpha4beta2 receptors may mediate this response. Using the 86Rb+ efflux assay, calcium effects on receptor activation, desensitization induced by high, activating and low, subactivating concentrations of agonist, and recovery from desensitization were examined. Effects of calcium on the kinetics of ligand binding were also investigated. Calcium modulated receptor activation by increasing the maximal response to nicotine in a concentration-dependent manner, without affecting the EC50 of nicotine. Barium, but not magnesium, mimicked the effects of calcium on receptor activation. The increase in receptor activation could not be explained by changes in the ratio of activatable to desensitized receptors as assessed by the kinetics of ligand binding. Desensitization following activation was unaffected by calcium. Calcium, barium, and magnesium, however, increased the potency of nicotine for desensitization induced by exposure to low, subactivating concentrations of nicotine. Recovery from desensitization was not modulated by calcium. These data suggest that calcium modulates various functional aspects of nicotinic receptors from mouse brain and may do so via different mechanisms.

Differential agonist inhibition identifies multiple epibatidine binding sites in mouse brain.

The binding of [3H]epibatidine, an alkaloid isolated from the skin of an Ecuadorean tree frog, was measured both in brain regions dissected from mouse brain and in tissue sections. Binding to each of 12 brain areas was saturable, but apparently monophasic; no indication of multiple binding sites was obtained. However, inhibition of epibatidine binding by nicotine, acetylcholine, methylcarbachol and cytisine in olfactory bulbs revealed a biphasic pattern consistent with the presence of two sites differentially sensitive to inhibition by these nicotinic agonists. Cytisine displayed the greatest difference in inhibitory potency between the two apparent sites. Subsequent analysis of the inhibition of epibatidine binding by cytisine in membranes prepared from 12 brain areas also suggested the presence of two sites in each brain region. The estimated potency of cytisine at each site was similar in each brain region. However, the proportion of [3H]epibatidine binding sites that were more sensitive to inhibition by cytisine and those sites less sensitive to inhibition by this agonist varied markedly among the brain regions. Quantitative autoradiographic analyses of mouse brain revealed pattern of [3H]epibatidine binding sites less sensitive to inhibition by cytisine that differed markedly from the pattern obtained with [3H]nicotine. Among brain regions demonstrating substantial sites less sensitive to cytisine inhibition were the accessory olfactory nucleus, medial habenula, interpeduncular nucleus, fasciculus retroflexus, superior colliculus, inferior colliculus and the pineal gland. The results indicate that epibatidine binds to at least two distinct nicotinic sites in mouse brain that may represent different nicotinic receptor subtypes, one of which appears to be identical to that measured by the binding of other agonists such as nicotine or cytisine.

Use of the MQoL-HIV with asymptomatic HIV-positive patients.

The purpose of this study was to determine the appropriateness of the recently developed Multidimensional Quality of Life Questionnaire for HIV/AIDS (MQoL-HIV) as a measure of quality of life (QoL) in cases of asymptomatic human immunodeficiency virus (HIV) infection. The MQoL-HIV is a 40-item instrument measuring ten domains (mental health, physical health, physical functioning, social functioning, social support, cognitive functioning, financial status, partner intimacy, sexual functioning and medical care) relevant to HIV infection. An overall QoL score, the MQoL-HIV Index, is a weighted composite of two domain scores. In a sample of 216 HIV-infected men and women, the MQoL-HIV distinguished acquired immune deficiency syndrome (AIDS), symptomatic and asymptomatic cases in overall QoL and in seven individual QoL domains. The index was responsive to perceived QoL changes over 5.5 months (r = 0.52). We also found the MQoL-HIV was less susceptible to ceiling effects in asymptomatic cases than was the Medical Outcomes Study (MOS) SF-20. These results suggest that the MQoL-HIV is a valid and reliable measure of QoL for both asymptomatic and symptomatic HIV infection.

Development of the multidimensional index of life quality. A quality of life measure for cardiovascular disease.

OBJECTIVES: The purpose of this study was to design a multidimensional measure of health-related quality of life appropriate for patients with cardiovascular disease that was psychometrically sound, brief, and easy to administer. METHODS: Qualitative interviews conducted with healthy subjects and patients with cardiovascular diseases identified nine major quality of life domains. Based on the responses of 129 cardiovascular disease patients recruited from hospitals and clinics, a criterion-based approach was used to select 35 questionnaire items that best tapped these domains. Psychometric properties of the Multidimensional Index of Life Quality (MILQ) were tested with a sample of 348 patients with various cardiovascular diseases. RESULTS: Cronbach's alpha was 0.76 or higher for eight of the nine MILQ domains. Test-retest reliability coefficients were 0.73 or greater in all but two domains. Individual domain scores as well as a weighted overall quality of life index were correlated highly with self-assessed health and the number of heart-related symptoms. CONCLUSIONS: The Multidimensional Index of Life Quality is a psychometrically reliable and valid instrument for measuring quality of life in patients with cardiovascular diseases. The MILQ also may be a suitable measure for other types of chronic diseases.

Quality of Medicare-reimbursed home health care.

We investigated the prevalence of quality of care deficiencies in 4,324 Medicare-reimbursed episodes of care provided by 47 home health agencies. The quality of care protocol consisted of a process-oriented, systematic record review by a trained nurse reviewer. Results suggest that an estimated 14.4% of home health care episodes had quality deficiencies with the potential for or actual adverse effects on the patient. Multivariate analyses revealed that the complexity of patients' needs increased the likelihood and severity of the quality problems. Agency ownership was not related to risk of a quality problem, but regional variation in agency effects was observed. Specific problem areas were identified that suggested several ways that home health care could be improved.

Monitoring body-core temperature from the trachea: comparison between pulmonary artery, tympanic, esophageal, and rectal temperatures.

INTRODUCTION: We designed an endotracheal tube (ETT) for acquiring body-core temperature from the trachea. This ETT had two temperature sensors, one attached to the inside surface of the cuff, the other mounted on the ETT shaft underneath the cuff. The ETT was evaluated in vitro and in dogs to determine: 1) optimal position of temperature sensors and 2) the responsiveness, accuracy, and resistance to ventilatory artifacts. METHODS: In vitro. An artificial trachea assessed the response-time and accuracy of ETT temperature sensors to abrupt temperature changes and ventilatory flow-rates. In vivo. Body temperature in 5 dogs was lowered to approximately 26 degrees C then elevated toward 39 degrees C using a heat exchanger during carotid-jugular bypass. ETT temperature measurements were compared simultaneously with those from the artificial trachea (in vitro) or from the pulmonary artery, tympanic cavity, esophagus, and rectum of dogs using dry and humidified gas. RESULTS: Cuff temperature sensor responded quickly and accurately to temperature changes and was less prone than the tube sensor to ventilatory and humidity artifacts. During carotid-jugular bypass, in vivo tube and cuff mean temperatures averaged 1.4 degrees C and 0.36 degree C lower, respectively, than pulmonary artery temperatures. There were no statistical differences (P > 0.05) between cuff temperatures and those measured from the pulmonary artery, tympanic cavity, esophagus, and rectum. Heating and humidifying the inspiratory gas of dogs with a water-bath humidifer or heat moisture exchanger (HME) had minimal effects on the cuff temperature sensor. An in-line HME increased in vivo tube temperature from baseline values by 1.13 +/- 0.80 degree C, while cuff temperature increased by 0.21 +/- 0.24 degree C. CONCLUSION: The cuff of the ETT is a reliable site for measuring body-core temperature in intubated patients.

A self-efficacy scale for HIV risk behaviors: development and evaluation.

To measure self-efficacy with respect to risk behaviors for HIV infection, a set of questionnaire items was developed regarding condom use, drug use with friends, and negotiations with potential sex partners. These items were tested with a sample of Latinos aged 14 to 22 years in two New England cities. A nine-item self-efficacy scale was found to have a high level of internal consistency (Cronbach's alpha = .77). Reliability coefficients were similar for men, women, and both English- and Spanish-speaking respondents. Strong associations with recent performance accomplishments, as specified in Bandura's social cognitive theory, support the construct validity of the scale.

Antibiotic prophylaxis during clean neurosurgery: a large, multicenter study using cefuroxime.

Cefuroxime is a second-generation cephalosporin with in vitro activity against the organisms that are commonly associated with neurosurgical wound infections. Other properties of cefuroxime are an elimination half-life of 1.3 hours, which yields prolonged serum concentrations, and its ability to penetrate the blood-brain barrier in proportion to the degree of inflammation. A prospective, multicenter, open-label study was conducted to evaluate the efficacy and safety of cefuroxime for antibiotic prophylaxis in patients undergoing clean neurosurgery. Cefuroxime 1.5 g was given intravenously 25 to 60 minutes before surgery; for procedures lasting more than 3 hours, cefuroxime 750 mg was given intravenously 8 hours after the initial dose. Patients were examined before surgery, daily during hospitalization, and at 8 weeks after surgery. A total of 956 adults were enrolled in the study. The most common procedures in study patients were laminectomy (41.8% of patients) or craniotomy (24.3%), and the mean duration of surgery was 3.2 hours. Infection occurred in 2 (0.3%) of 592 assessable patients by the time of discharge and in 1 additional patient by the 8-week follow-up evaluation for a total of 3 (0.5%) of 560 assessable patients. Drug-related adverse events occurred in 5 (0.5%) of 956 patients. These results indicate that antibiotic prophylaxis with cefuroxime is associated with a low incidence of postoperative wound infection and is well tolerated in patients undergoing clean neurosurgery.

Ambulatory surgical hemorrhoidectomy--a solution to postoperative urinary retention?

PURPOSE: The most frequent complication of surgical hemorrhoidectomy is urinary retention. This study evaluates the incidence of urinary retention in a series of patients undergoing surgical hemorrhoidectomy in an ambulatory setting. METHODS: The records of all patients undergoing anorectal surgical operative procedures during the calendar year 1990 were reviewed, with particular emphasis on urinary retention and other postoperative complications. RESULTS: Of 201 patients undergoing full surgical hemorrhoidectomy by Colon and Rectal Clinic, 91 percent had operations performed on an ambulatory basis (discharge less than four hours following surgery). Of these 190 patients, only 1 (0.53 percent) required urinary catheterization during the postoperative period. CONCLUSIONS: The ambulatory setting, when combined with careful patient education and perioperative fluid restriction, allows surgical hemorrhoidectomy to be performed with a very low incidence of urinary retention to the benefit of both patient and surgeon.

Do blacks and whites differ in their use of health care for symptoms of coronary heart disease?

OBJECTIVES: The purpose of this study was to identify the role of race in seeking and receipt of care for symptoms of coronary heart disease. METHODS: Data on medical care, sociodemographic characteristics, symptoms, risk factors, income, and insurance were collected in a telephone interview for a random sample of 2030 Black and White adults in inner-city Boston. Rates of care-seeking for symptoms, amounts of delay in seeking care, and rates of receipt of care were compared for Blacks and Whites after adjustment for other characteristics. RESULTS: Before and after adjustment for other factors, Blacks and Whites were equally likely to seek care. Average delay time was shorter for Blacks, particularly Black women. With the exception of a lower rate of referral to cardiologists among Blacks, receipt of care was similar for Blacks and Whites who sought medical attention for symptoms. CONCLUSIONS: In an urban population of Blacks and Whites who were similar in socioeconomic status and access to medical care, there were few racial differences in coronary heart disease-related care patterns.